Studies on in vitro modulatory effects to base excision repair enzymes induced by small molecule binding to Deaminated CAG repeat hairpin.

Base Excision Repair (BER) pathway is correlated with nucleotide repeat instability. In this report, we investigated the modulatory effects of a DNA-binding small molecule, naphthyridine azaquinolone (NA), towards BER in an in vitro system. Thermal melting analyses demonstrated binding of NA to deaminated 5'-CAG-3'/5'-CAG-3' triads in DNA. Furthermore, binding of NA to the deaminated CAG repeat hairpin was found to partially inhibit UNG2- and APE1-catalyzed reaction, suggesting a potential mechanism for NA-induced CAG repeat contraction via BER pathway.